The long-term objective of this proposal is to investigate the enzootiology of the Lyme disease spirochete Borrelia burgdorferi in the southeastern United States, particularly Georgia, South Carolina, and Florida. Statistics on number of human Lyme disease cases in the South are unreliable and current surveillance is inadequate. Borrelia burgdorferi is found in several species of rodents and is widely spread along coastal South Carolina, Georgia, and Florida (northern SC to Cape Canaveral, FL) and occurs inland. A competent vector tick that bites humans, Ixodes scapularis, is naturally infected with B. burgdorferi in Georgia, South Carolina, and Florida and has a wide geographical distribution. I minor is also naturally infected and may serve as a maintenance vector among rodents and birds. Another perhaps parallel cycle exists in central Georgia and involves a genetically different strain of B. burgdorferi, cottontail rabbits, and Ixodes dentatus. The latter feeds primarily on rabbits, but occasionally bites humans. I scapularis feeds on rabbits and humans and might serve as a "bridge" vector to humans. A necessary first step in assessing human risk of Lyme disease is to investigate the enzootiology of Lyme borreliosis. Therefore, specific aims of this proposal include (1) determining the geographic distribution (foci) of B. burgdorferi (2) establishing which tick species transmit the spirochete and its prevalence in ticks and vertebrates, (3) determining which vertebrate species serve as tick hosts and as reservoir hosts to the spirochete (4) examining the genetic heterogeneity among B. burgdorferi sensu lato from Georgia, South Carolina, and Florida, and (5) determining if genetic differences in the southern strains are correlated with infectivity and pathogenicity to mammal and lizard species. Field-collected ticks and vertebrates will be examined for spirochete infections by several methods (monoclonal antibodies, polymerase chain reaction, isolation of B. burgdorferi in BSKII culture medium). Spirochetes will be characterized by the above methods and by SDS-PAGE protein profiles and genomic macrorestriction analysis of whole cell DNA. Infectivity and pathogenicity of selected B. burgdorferi strains will be determined by inoculation or tick bite of selected spirochete strains to selected laboratory animals.